We propose to develop novel bioadhesive microspheres which will serve as oral drug delivery systems for diseases of the gastrointestinal tract. This project involves the correlation between in vitro bioadhesion properties measured by using specialized tensile technique and in vivo retention times as well as development of delivery systems for drugs used in the treatment of inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn's disease. An important hypothesis to be tested include the concept that protonated carboxyl groups are vital for bioadhesion, and that these may function effectively on flexible chains such as swollen hydrogel polymer as well as on more rigid chains on bioerodible thermoplastic polymers. To address this issue, we plan to couple three investigative approaches. First, we will conduct direct surface characterization of the various microspheres to quantify the amount of carboxyl groups or any other mucin specific ligands. These studies will be done by using ESCA as well as ATIR. Second, an electrobalance will be used to make direct in vitro measurements of the adhesive forces between polymer microspheres and representative tissues of the GI tract, while maintaining regional pH environments. Third, the direct in vivo evaluation of adhesive, radio-opaque microspheres, retained beyond the normal time of gastrointestinal transit, will be studied through serial X-ray imaging of animals. Overall, the work will consist of the following phases: polymer selection from a pool of synthetic and naturally-occurring polymers; synthesis and characterization of the selected materials; preparation of bioadhesive microspheres carrying barium sulfate, 5-aminosalicylic acid or a combination thereof; bioadhesion studies in vitro; bioadhesion studies in vivo: and in vivo delivery system efficiency tests.